Site-Specific Integration of Amino Acid Fragments into Cyclic Peptides

Christopher J. White, Jennifer L. Hickey, Conor C. G. Scully, and Andrei K. Yudin*

Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada

J. Am. Chem. Soc., 2014, 136 (10), pp 3728–3731

DOI: 10.1021/ja412256f

Publication Date (Web): February 17, 2014

ayudin@chem.utoronto.ca

Abstract

The concept of site-specific integration of fragments into macrocyclic entities has not yet found application in the realm of synthetic chemistry. Here we show that the reduced amidicity of aziridine amide bonds provides an entry point for the site-specific integration of amino acids and peptide fragments into the homodetic cyclic peptide architecture. This new synthetic operation improves both the convergence and divergence of cyclic peptide synthesis.

Supporting Information

Experimental details, optimization data, characterization data, HPLC traces, and ¹H and ¹³C NMR spectra of all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org.

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Site-Specific Integration of Amino Acid Fragments into Cyclic Peptides

Abstract

Supporting Information

PDF

Cyclizing Pentapeptides: Mechanism and Application of Dehydrophenylalanine as a Traceless Turn-Inducer

Solution- and Solid-Phase Macrocyclization of Peptides by the Ugi–Smiles Multicomponent Reaction: Synthesis of N-Aryl-Bridged Cyclic Lipopeptides

Applications of Convertible Isonitriles in the Ligation and Macrocyclization of Multicomponent Reaction-Derived Peptides and Depsipeptides

Chemoselective Ketone Synthesis by the Addition of Organometallics to N-Acylazetidines

Multicomponent Synthesis of Cyclic Depsipeptide Mimics by Ugi Reaction Including Cyclic Hemiacetals Derived from Asymmetric Organocatalysis

Diastereoselective Synthesis of α-Quaternary Aziridine-2-carboxylates via Aza-Corey–Chaykovsky Aziridination of N-tert-Butanesulfinyl Ketimino Esters

Macrocyclization Reactions: The Importance of Conformational, Configurational, and Template-Induced Preorganization

Macrocyclization of Peptide Side Chains by the Ugi Reaction: Achieving Peptide Folding and Exocyclic N-Functionalization in One Shot

Aminocatalysis-Mediated on-Resin Ugi Reactions: Application in the Solid-Phase Synthesis of N-Substituted and Tetrazolo Lipopeptides and Peptidosteroids

Stereoelectronic Chameleons: The Donor-Acceptor Dichotomy of Functional Groups

Ring-Expansion Approach to Medium-Sized Lactams and Analysis of Their Medicinal Lead-Like Properties

Non-covalent Interactions for the Preparation of Pseudopeptidic Synthetic Compounds and Materials

The effect of backbone flexibility on site-selective modification of macrocycles

The Synthesis of Structurally Diverse Macrocycles By Successive Ring Expansion

The Synthesis of Structurally Diverse Macrocycles By Successive Ring Expansion

Solid phase synthesis and ligative processing of photocaged aziridine-2-carbonyl-terminated peptides

Recent progress on using BINOLs in enantioselective molecular recognition

Bidirectional macrocyclization of peptides by double multicomponent reactions

Aziridine electrophiles in the functionalisation of peptide chains with amine nucleophiles

Macrocycles: lessons from the distant past, recent developments, and future directions

The synthesis of head-to-tail cyclic sulfono-γ-AApeptides

Library construction, selection and modification strategies to generate therapeutic peptide-based modulators of protein–protein interactions

Combinatorial Chemistry Online Volume 16, Issue 5, May 2014

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Site-Specific Integration of Amino Acid Fragments into Cyclic Peptides

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